In situ sintering study of model nickel catalysts

Master Thesis


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University of Cape Town

Lipid catabolism plays a significant role in the survival of M.tb inside the host. The development of analytical techniques such as gas chromatography mass spectroscopy (GCMS) and liquid chromatography mass spectroscopy (LC-MS) has become popular as metabolomics tools in the study of such catabolic pathways. The development of biomarkers and internal standards to perform quantitative and qualitative analysis of metabolites in the catabolic pathway would be an attractive tool. Thus, cholesterol derivatives were synthesized as thia-, fluoro- and deuterium labeled analogs. Sulfur was incorporated into cholesterol at positions, C3 as well as C23. The 3â-mercaptocholest-5-ene was synthesized to block the initial stage of cholesterol catabolism and evaluate whether side chain degradation can still occur. Fluorine was integrated into the cholesterol backbone at C3 to evaluate the side-chain degradation in the absence of cholesterol oxidase activity. Steroids with fluorine at C6 are known to have good biological activity and were for this reason also synthesized. Deuterium labeled compounds were synthesized and used as internal standards for GC-MS analysis. As an alternative to cholesterol catabolism, fatty acids like stearic acid are important in producing building blocks for long chain mycolic acids which provides protection to the mycobacterium. For this reason thiastearic acid derivatives were synthesized and evaluated as biomarkers.

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